Dept of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara 06100, Turkey.
Pediatr Nephrol. 2012 Jan;27(1):115-21. doi: 10.1007/s00467-011-1942-6. Epub 2011 Jul 24.
We report the molecular findings for the CTNS gene in 12 Turkish cystinosis patients aged 7-29 years. All presented initially with severe failure to thrive, polyuria, and polydipsia. Cystinosis was diagnosed at age 1 month to 9 years. Seven patients reached end-stage renal failure at ages ranging from 6.5 to 15 years. Whereas three of the remaining five have renal Fanconi syndrome with proteinuria, two have had kidney failure of varying degrees. Molecular analyses involved an initial multiplex polymerase chain reaction (PCR) to determine the presence or absence of the 57-kb northern European founder deletion in CTNS, followed by sequencing of the ten coding exons of CTNS. Comprehensive mutation analysis verified that none of the 12 patients carried the common 57-kb deletion. We identified four previously reported nucleotide variations associated with cystinosis and five new variants: a 10-kb deletion, three missense variants, and a nucleotide substitution in a potential branch point site of intron 4. This study is the first molecular analysis of Turkish cystinosis patients and provides guidance for the molecular diagnosis of cystinosis in this population.
我们报告了 12 名土耳其胱氨酸病患者 CTNS 基因的分子发现，这些患者年龄在 7 至 29 岁之间。所有患者最初均表现为严重的生长不良、多尿和多饮。胱氨酸病在 1 个月至 9 岁时被诊断出。7 名患者在 6.5 至 15 岁时进展为终末期肾衰竭。而其余 5 名患者中的 3 名患有伴有蛋白尿的肾性范可尼综合征，2 名患者的肾功能有不同程度的衰竭。分子分析包括初步的多重聚合酶链反应 (PCR) 以确定 CTNS 中是否存在或不存在 57kb 北欧创始性缺失，然后对 CTNS 的十个编码外显子进行测序。全面的突变分析证实，这 12 名患者均未携带常见的 57kb 缺失。我们发现了与胱氨酸病相关的四个先前报道的核苷酸变异和五个新变异：10kb 缺失、三个错义变异和内含子 4 中潜在分支点位点的核苷酸取代。这项研究是对土耳其胱氨酸病患者的首次分子分析，为该人群中胱氨酸病的分子诊断提供了指导。
